The objective of the research is synthesis and evaluation of 8-deazafolic acid analogs for their ability to act as antifolates via interference with folate utilization or transport. During the project year the synthesis of 8,10-dideazafolate was carried out. The compound was found to be about 1/10 as potent an inhibitor of Streptococcus faecium growth as was 8-deazafolic acid or methotrexate. The potency range suggests the compound is still of therapeutic potential in vivo. Scale-up preparation is in progress. Similar methods are being applied to the synthesis of 8-deazahomofolic and 8-deazafolic acids. BIBLIOGRAPHIC REFERENCES: J. DeGraw, V. Brown, R.L. Kisluik, and Y. Gaumont. Deaza Analogues of Folate. Abstr. Med. Chem. Congress, Paris 1976 (Abstract, in press).